The cytokine interluekin-I (IL-I) has been shown to inhibit insulin secretion and destroy islets by a mechanism that involves the expression of inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO). Insulin containing B-cells, selectively destroyed during the development of autoimmune diabetes, appear to by the cellular source of iNOS following treatment of islets with IL-I. In this study we have evaluated the presence of type 1 IL-I receptors on primary B-cells. The interluekin-1 receptor angatonist protein (IRAP) inhibits IL-1B-induced nitrite formation by the insulinoma cell line RINm5F, isolated islets, and primary a-cells purified by fluorescenceactivated cell sorting (FACS). Il-IB-induced inhibition of glucose-stimulated insulin secretion by intact islets and purified a-cells is also prevented by IRAP. In a concentration-dependent manner IRAP prevents IL-I-induced PGE2 production by islets. IRAP appears to prevent IL-I-induced inhibition of insulin secretion by blocking the expression of iNOS as determined by immunoprecipitation of iNOS from both islets and FACS purified a-cells. Antiserum specific for the type I IL-I receptor also inhibits IL-I-induced nitrite formation by RINm5F cells in a concentration-dependent fashion. These results provide evidence for the presence of type I IL-I receptors on primary a-cells.